POS0979 THE GLUCOCORTICOID TOXICITY INDEX-METABOLIC DOMAINS: AN ABRIDGED VERSION OF THE GLUCOCORTICOID TOXICITY INDEX
Authors: N. Patel, D. Jayne, P. A. Merkel, P. Bekker, Y. Zhang, M. Stone, H. Yue, J. H. Stone
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Measurement of glucocorticoid (GC) toxicity is critical to efforts to reduce it. In clinical trials, the Glucocorticoid Toxicity Index (GTI)<sup>[1]</sup> measures toxicity effectively using two scores, the Cumulative Worsening Score (CWS) and the Aggregate Improvement Score (AIS). In clinical practice, high patient volumes limit time available to perform the full GTI. An abbreviated GTI version – the GTI-Metabolic Domains (GTI-MD) – may address this issue by including only data that are collected routinely at clinic visits, requiring no additional physician time. The GTI-MD includes four domains: Body Mass Index, Glucose Tolerance, Blood Pressure, and Lipid Metabolism. <h3>Objectives</h3> We evaluated the correlations between the GTI-MD, overall GTI scores, and the remaining GTI domains to determine if the GTI-MD differentiates patients effectively according to GC toxicity. <h3>Methods</h3> We used data from ADVOCATE<sup>[2]</sup>, a phase 3 trial in which avacopan replaced a standard GC taper in ANCA-associated vasculitis, to test the correlation of the GTI-MD with overall GTI scores. We evaluated the ability of the GTI-MD to differentiate the treatment groups by GC toxicity, comparing GTI-MD scores between groups at weeks 13 and 26. <h3>Results</h3> The abilities of the full GTI domains to differentiate the treatment groups according to GC toxicity have been reported<sup>[3]</sup>. The Spearman rank correlation coefficient for the GTI-MD CWS with GTI CWS was 0.78 (p&lt;0.0001). The corresponding correlation for the AIS was 0.73 (p&lt;0.0001). The GTI-MD distinguished the two groups by GC toxicity at both 13 and 26 weeks (<b>Table 1</b>). The mean GTI-MD CWS was lower in the avacopan group, consistent with less toxicity (15.9 versus 23.0 at 13 weeks [p=0.001]; 26.7 versus 31.7 at 26 weeks [p=0.009]). The GTI-MD AIS values were also consistent with less toxicity in the avacopan group (2.5 versus 13.0 at 13 weeks [p=0.0003], 4.4 versus 10.1 at 26 weeks [p=0.03]). Contributions of the four GTI-MD domains were balanced (<b>Figure 1</b>). A GTI-MD score of zero correlated with low toxicity in other domains. <h3>Conclusion</h3> The GTI-MD correlated well with the full GTI in ADVOCATE and may be incorporated readily into routine clinic workflows. Additional studies will be required to determine how effectively the GTI-MD predicts certain long-term GC toxicities such as osteonecrosis, bone fractures, infection, and death, and to understand how the instrument performs in other types of settings and study designs. Utilization of the GTI-MD may help clinicians monitor GC toxicity longitudinally, with the goals of preventing the burden of chronic, treatment-related morbidity, and reducing long-term costs to health systems. <h3>References</h3> [1]Stone JH, McDowell PJ, Jayne DRW et al. The glucocorticoid toxicity index (GTI): measuring change in glucocorticoid toxicity over time. <i>Seminars Arthr Rheum</i> 2022; 55:152010. [2]Jayne DRW, Merkel PA, Schall TJ et al. Avacopan for the treatment of ANCA-associated vasculitis. <i>N Engl J Med</i> 2021; 384:599-609. [3]Patel NJ, Jayne DRW, Merkel PA et al. Glucocorticoid Toxicity Index Scores by Domain in Patients with ANCA-Associated Vasculitis Treated with Avacopan versus Standard Prednisone Taper: post-hoc analysis of data from the ADVOCATE trial. <i>Lancet Rheumatol</i> 2023 (in press). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Naomi Patel: None declared, David Jayne Speakers bureau: David Jayne reports lecture fees from Amgen, Vifor., Consultant of: Astra-Zeneca, BMS, Boehringer-Ingelheim, Chemocentryx, GSK, NICE, Novartis, Otsuka, Roche/Genentech, Takeda, UCB &amp; Vifor., Grant/research support from: Commercial research grants from GSK, Roche/Genentech, Peter A Merkel Consultant of: consulting with AbbVie, AstraZeneca, Boeringher-Ingelheim, Bristol-Myers Squibb, ChemoCentryx, CSL Behring, Dynacure, EMDSerono, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, Immagene, InflaRx, Jannsen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, Pfizer, Regeneron, Sparrow, Takeda, Talaris, Grant/research support from: research support from AbbVie, AstraZeneca, Boeringher-Ingelheim, Bristol-Myers Squibb, ChemoCentryx, Eicos, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Sanofi, Takeda, Pirow Bekker Shareholder of: ChemoCentryx, Inc, Consultant of: ChemoCentryx, Inc., Employee of: ChemoCentryx, Inc., Yuqing Zhang: None declared, Martha Stone Shareholder of: Steritas, LLC, Employee of: Steritas, LLC, Huibin Yue Shareholder of: Amgen, Inc., Employee of: ChemoCentryx, Inc., Amgen, Inc., John H. Stone Shareholder of: Steritas, LLC, Paid instructor for: ChemoCentryx, Roche/Genentech, Sanofi, Bristol-Myers Squib, Horizon, Consultant of: consulting fees from ChemoCentryx, Roche/Genentech, Sanofi, Bristol-Myers Squib, AbbVie, InflaRx, Kyverna, Novartis, Q32Bio, Steritas, Zenas, Horizon, Grant/research support from: commercial research grants from Roche/Genentech, Sanofi, Bristol-Myers Squib; non-commercial research grants from NIH/NIAID.